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Background: Up to 25% of elderly humans have proteinuria, often associated with underlying lesions. Data concerning the presence of proteinuria in elderly dogs is scarce., Objectives: To describe the presence and persistence of proteinuria and to compare urinary protein : creatinine ratio (UPC) between free catch and cystocentesis urine samples in apparently healthy elderly dogs., Animals: Hundred apparently healthy elderly dogs., Methods: Prospective study. Owners of 100 elderly dogs were asked to collect 2 free catch urine samples. Dogs were considered healthy based on owner's perception and an age chart, based on ideal bodyweight, was used to define dogs as senior or geriatric. UPC of urine collected by free catch and cystocentesis were compared. Overt proteinuria and borderline proteinuria were defined as UPC >0.5 and between 0.2 and 0.5, respectively, if examination of sediment did not explain proteinuria. Proteinuria was considered persistent if present at both sampling times., Results: At baseline, 71 owners succeeded in collecting urine. Eleven percent of dogs had overt proteinuria, 14% were borderline proteinuric, and 75% nonproteinuric. Thirty-seven repeated urine samples, with a median time interval of 31 days (range 10-90), were available. Nineteen percent of dogs had a persistently increased UPC (>0.2), with persistent overt proteinuria present in 8%. A strong correlation (ρ = 0.88) was found between UPC of urine collected by free catch and cystocentesis., Conclusions and Clinical Importance: As 19% of study dogs had persistent proteinuria, our findings emphasize that measurement of proteinuria should be part of geriatric health screening. For UPC in dogs, free catch urine provides a good alternative to cystocentesis., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Serum cystatin C (sCysC) is used as biomarker for glomerular filtration rate (GFR). The effects of diabetes mellitus (DM) on renal function in dogs are unclear. Some renal variables have been evaluated in dogs with hyperadrenocorticism (HAC), but not sCysC., Objectives: The purpose of this study was the validation of a particle-enhanced nephelometric immunoassay (PENIA) for measuring canine sCysC, and to assess renal function in dogs with DM or HAC., Methods: A PENIA was analytically validated for canine sCysC by determining imprecision and linearity. In a longitudinal 6-month study, renal function of 14 DM dogs was assessed, using serum creatinine, GFR, urinary protein-to-creatinine (UPC) ratio, urinary markers, systolic blood pressure (SBP), and sCysC, and compared to 17 healthy dogs at baseline. Furthermore, sCysC was measured at initial presentation and during a 12-month follow-up in 22 HAC dogs., Results: The sCysC intra- and inter-assay variation coefficients were < 8% and highly linear (r = .997). About 33% and 67% of DM dogs had persistent proteinuria and systemic hypertension, respectively, but there were no significant differences in GFR, UPC, and urinary markers over time, and compared with healthy dogs at initial presentation. Serum CysC decreased significantly (P < .05) over time within the DM group. It did not change significantly over time within the HAC group., Conclusions: A PENIA measured sCysC linearly and precisely. There were no clinically relevant renal alterations over time in dogs with DM, although persistent proteinuria was observed. In dogs with HAC, sCysC measurement was not useful, although significant GFR changes occurred over time., (© 2016 American Society for Veterinary Clinical Pathology.)

Dogue de Bordeaux dog has been reported to be predisposed to a familial glomerulonephropathy that displays some morphological modifications reported in focal and segmental glomerulosclerosis. Prevalence of quantitatively abnormal renal proteinuria was recently reported to be 33% in this breed. The nature of the proteinuria was assessed by sodium dodecyl sulfate-agarose gel electrophoresis and determinations of urinary markers (urinary retinol-binding protein, urinary N-acetyl-β-glucosaminidase, urinary albumin and urinary immunoglobulin G) on stored specimens. Diagnostic performances of sodium dodecyl sulfate-agarose gel electrophoresis to identify dogs with elevated urinary biomarkers were assessed. Samples from 102 adult Dogue de Bordeaux dogs (47 non-proteinuric [urine protein-to-creatinine ratio ≤ 0.2], 20 borderline-proteinuric [0.2< urine protein-to-creatinine ratio ≤ 0.5] and 35 proteinuric dogs [urine protein-to-creatinine ratio >0.5]) were used, of which 2 were suffering from familial glomerulonephropathy. The electrophoretic protein patterns, for all but one proteinuric dog, were indicative of a glomerular origin and, in all dogs, the urinary albumin concentration related to creatinine concentration and the urinary immunoglobulin G concentration related to creatinine concentration were above the upper limit of the reference interval established for the breed. Sensitivity and specificity of sodium dodecyl sulfate-agarose gel electrophoresis identifying dogs with elevated urinary albumin concentration were 94% and 92%, respectively, while diagnostic performance of sodium dodecyl sulfate-agarose gel electrophoresis in detecting dogs with elevated urinary immunoglobulin G concentration yielded sensitivity and specificity of 90% and 74%, respectively. These results suggest that all proteinuric and some borderline-proteinuric Dogue de Bordeaux dogs likely have underlying glomerular lesions and that sodium dodecyl sulfate-agarose gel electrophoresis and urinary markers might be useful to screen dogs with borderline-proteinuria. Additional investigations are warranted to assess if these findings are related to the familial glomerulonephropathy.

Objective: To assess vascular changes induced by hyperadrenocorticism of hyperplastic adrenal glands in dogs via contrast-enhanced ultrasonography., Animals: 12 dogs with pituitary-dependent hyperadrenocorticism (PDH) and 7 healthy control dogs ≥ 7 years old., Procedures: Dogs were assigned to the PDH and control groups and to small-breed (n = 6), medium-breed (4), and large-breed (9) subgroups. Contrast-enhanced ultrasonography of both adrenal glands in each dog was performed with IV injections of contrast agent. Time-intensity curves for the adrenal cortex, adrenal medulla, and ipsilateral renal artery of both adrenal glands were generated. Perfusion variables (time to peak [TTP], upslope of wash-in phase, and downslope of washout phase) were calculated., Results: Contrast-enhanced ultrasonography revealed no qualitative difference between PDH and control groups. Quantitatively, TTPs were longer in the adrenal cortex and adrenal medulla of the PDH group, compared with values for the control group, particularly in the adrenal cortex and adrenal medulla of the small-breed subgroup. Washout downslopes were lower for the renal artery, adrenal cortex, and adrenal medulla of the small-breed subgroup between the PDH and control groups. No other perfusion variables differed between groups., Conclusions and Clinical Relevance: Contrast-enhanced ultrasonography of the adrenal glands in dogs with PDH revealed a delayed TTP in the adrenal cortex and adrenal medulla, compared with values for control dogs. Contrast-enhanced ultrasonography was able to detect vascular changes induced by hyperadrenocorticism. Further studies are needed to evaluate whether reference ranges for clinically normal dogs and dogs with PDH can be determined and applied in clinical settings.

Objective: To determine the feasibility of quantitative contrast-enhanced ultrasonography (CEUS) for detection of changes in renal blood flow in dogs before and after hydrocortisone administration., Animals: 11 Beagles., Procedure: Dogs were randomly assigned to 2 treatment groups: oral administration of hydrocortisone (9.6 mg/kg; n = 6) or a placebo (5; control group) twice a day for 4 months, after which the dose was tapered until treatment cessation at 6 months. Before treatment began and at 1, 4, and 6 months after, CEUS of the left kidney was performed by IV injection of ultrasonography microbubbles. Images were digitized, and time-intensity curves were generated from regions of interest in the renal cortex and medulla. Changes in blood flow were determined as measured via contrast agent (baseline [background] intensity, peak intensity, area under the curve, arrival time of contrast agent, time-to-peak intensity, and speed of contrast agent transport)., Results: Significant increases in peak intensity, compared with that in control dogs, were observed in the renal cortex and medulla of hydrocortisone-treated dogs 1 and 4 months after treatment began. Baseline intensity changed similarly. A significant increase from control values was also apparent in area under the curve for the renal cortex 4 months after hydrocortisone treatment began and in the renal medulla 1 and 4 months after treatment began. A significant time effect with typical time course was observed, corresponding with the period during which hydrocortisone was administered. No difference was evident in the other variables between treated and control dogs., Conclusions and Clinical Relevance: Quantitative CEUS allowed detection of differences in certain markers of renal blood flow between dogs treated orally with and without hydrocortisone. Additional studies are needed to investigate the usefulness of quantitative CEUS in the diagnosis of diffuse renal lesions.

Renal function was assessed in 25 dogs with Cushing's syndrome and in 12 healthy controls. Routine renal parameters and glomerular filtration rate (GFR) were measured and urinary biomarkers such as urinary albumin (uALB), urinary immunoglobulin G (uIgG), and urinary retinol-binding protein (uRBP) were assessed by ELISA. Urinary N-acetyl-β-D-glucosaminidase activity (uNAG) was determined colorimetrically. All urinary markers were indexed to urinary creatinine concentration (c). Plasma exo- (Cl(exo)) and endo-iohexol (Cl(endo)) clearance were used to measure GFR. Based on a Mann-Whitney U test, urea and Cl(exo) did not differ, sCr was significantly lower, and UPC, uALB/c, uIgG/c, uRBP/c, uNAG/c and Cl(endo) were higher in the dogs with Cushing's syndrome when compared with controls. The findings indicate that glomerular and tubular function are both altered in dogs with Cushing's syndrome. Further longitudinal studies will be required to elucidate the pathogenesis of the changes in GFR., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Systemic hypertension and proteinuria are frequent complications in dogs with Cushing's syndrome and do not always resolve after treatment of hypercortisolism. Therefore, dogs with Cushing's syndrome may be at risk for renal dysfunction before and after treatment., Hypothesis/objectives: To assess renal function in dogs with ACTH-dependent hyperadrenocorticism (ADHAC) before and after treatment., Animals: A total of 19 dogs with ADHAC and 12 control dogs., Methods: Renal function was assessed before and at 1, 3, 6, and 12 months after treatment. Twelve dogs were treated with trilostane and 7 dogs by transsphenoidal hypophysectomy. Routine renal markers were measured and urinary albumin (uALB), immunoglobulin G (uIgG), and retinol-binding protein (uRBP) were assessed by ELISA. Urinary N-acetyl-β-D-glucosaminidase (uNAG) was determined colorimetrically. All urinary markers were indexed to urinary creatinine concentration (c). Plasma clearance of creatinine (Cl(creat)), exo-iohexol (Cl(exo)), and endo-iohexol (Cl(endo)) was used to measure glomerular filtration rate (GFR). Data were analyzed using a general linear model., Results: Serum creatinine and urea concentrations increased post-treatment, but remained within reference ranges. Plasma Cl(creat) and Cl(endo) were significantly lower post-treatment, whereas Cl(exo) was not different. Urinary protein-to-creatinine ratio (UPC), uALB/c, uIgG/c, and uRBP/c were decreased post-treatment, but at 12 months 5/13 dogs remained proteinuric. Urinary NAG/c did not change significantly., Conclusions and Clinical Importance: A decrease in GFR and persistent proteinuria post-treatment may warrant the clinician's attention. Future research including renal histopathology of dogs with persistent proteinuria or low GFR is needed to further assess renal outcome., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Our aim was to evaluate the influence of glucocorticoids on the adrenal gland using ultrasonography. Eleven healthy beagles were used in a prospective placebo-controlled study. All dogs received hydrocortisone at 10 mg/kg twice a day per os for 4 months or a gelatin capsule twice a day per os as a placebo. Clinical and endocrinologic examination of the dogs and ultrasonographic evaluation of adrenal echogenicity, shape, and measurement of the length and height of the cranial and caudal pole were performed at baseline (TO), at 1 (T1) and 4 months (T4) after the beginning of treatment, and 2 months after the end of the treatment including 1 month of tapering and 1 month without treatment (T6). The dogs were assigned randomly to the glucocorticoid (n = 6) and placebo groups (n = 5). At T1, the difference between the two groups for the height of the cranial and caudal pole was not ultrasonographically remarkable despite a statistically significant difference (P = 0.0165 and P = 0.0206). Decreased height and length of entire gland were observed at T4 (P < 0.0001, P = 0.0015, and P = 0.0035, respectively). Percentages of atrophy were variable between dogs. Both adrenal glands regained normal size and shape 1 month after cessation of glucocorticoid administration. As not all dogs developed marked adrenal gland atrophy and the degree of atrophy varied widely between individuals, ultrasonography cannot be the technique of choice to detect iatrogenic hypercortisolism. Ultrasonographic changes are reversible within 1 month after the end of glucocorticoid administration.

Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.

Urinary markers for renal dysfunction are gaining interest, but effects of sampling method, storage conditions, and urinary tract inflammation or infection on these markers are unclear. Therefore, the objectives of the current study were to determine the difference in urinary albumin (uALB), urinary retinol-binding protein (uRBP), and urinary N-acetyl-β-D-glucosaminidase (uNAG) concentrations in cystocentesis and voided samples and to investigate concentration changes after storage at -20°C and at -80°C. Effects of a protease inhibitor were also assessed in samples stored at -80°C for 12 months. In a pilot experiment, influence of in vitro hematuria, pyuria, and bacteriuria on the urinary markers was evaluated. A mixed model was used to calculate mean differences and 95% confidence intervals. Urinary ALB, uNAG, and uRBP concentrations were similar in voided and cystocentesis samples. After storage for 4 months at -20°C, uALB concentration was not affected, and uRBP concentration showed a mild and clinically irrelevant decrease, whereas uNAG activity was significantly lower compared with fresh samples. After storage for 12 months at -80°C, uALB and uRBP concentrations did not differ from fresh samples, but uNAG activity was severely decreased. Protease inhibitor addition did not preserve uNAG activity. Experimental hematuria, pyuria, and bacteriuria did not seem to affect urinary markers, although further research is needed.

Background: Blood urea nitrogen and serum creatinine concentrations only detect a decrease of > 75% of renal functional mass. Therefore, there is a need for markers that allow early detection and localization of renal damage., Hypothesis: Urinary albumin (uALB), C-reactive protein (uCRP), retinol binding protein (uRBP), and N-acetyl-beta-D-glucosaminidase (uNAG) concentrations are increased in dogs with chronic kidney disease (CKD) compared with healthy controls and in healthy older dogs compared with young dogs., Animals: Ten dogs with CKD, 10 healthy young dogs (age 1-3 years), and 10 healthy older dogs (age > 7 years) without clinically relevant abnormalities on physical examination, hematology, biochemistry, and urinalysis., Methods: Urinary markers were determined using an ELISA (uALB, uCRP, and uRBP) or a colorimetric test (uNAG). Results were related to urinary creatinine (c). The fixed effects model or the Wilcoxon rank sum test were used to compare the different groups of dogs., Results: uALB/c, uRBP/c, and uNAG/c were significantly higher in CKD dogs than in healthy dogs. No significant difference was found for uCRP, which was not detectable in the healthy dogs and only in 3 of the CKD dogs. Between the healthy young and older dogs, no significant difference was detected for any of the markers., Conclusion: The urinary markers uALB/c, uRBP/c, and uNAG/c were significantly increased in dogs with CKD compared with healthy controls. Additional studies are needed to evaluate the ability of these markers to detect renal disease before the onset of azotemia.